Should Advanced Age Preclude Surgical Treatment of Gastrointestinal Stromal Tumor?

Abstract

Introduction:

Surgical resection is a gold standard treatment for gastrointestinal stromal tumors (GISTs). It can be performed by minimally invasive surgery approach in most of the patients. It has been shown that advanced age is not a clear poor prognostic factor in patients who underwent surgery for GIST. We hypothesized that elderly patients undergo elective surgery less often compared to younger population. We aim to evaluate the safety, efficacy and oncological results of GIST treatment in the elderly population in our Medical Center.

Materials and Methods:

All patients who underwent surgery for GIST in Shamir Medical Center from January 1, 2016, to July 31, 2023, were included in the study. The patients were divided into 2 groups. Group 1 included patients younger than 75 years, while patients older than 75 years were included in Group 2. The groups were compared according to demographics, clinical and surgical parameters, complications, and pathology results.

Results:

Overall, 49 patients were included in the study. Group 1 included 28 patients and Group 2 included 21 patients. Group 2 patients more often underwent emergency surgery (52.4% versus 14.3%, P < .05) and had increased open surgery rate (19% versus 0%, P < .05). No difference between the groups was noted in surgical parameters, complications, and length of hospital stay. Tumor size, number of mitoses, level of ki67%, and involvement of surgical margins were not significantly different. However, in Group 2 patients, tumor size was larger and there was a trend toward higher rate of ki67 > 5%.

Conclusion:

Elderly patients with GIST are less frequently undergoing electively surgery and relatively often undergo open surgery. Frequency of complications is similar in elderly patients compares to younger patients group.

Introduction

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, usually diagnosed in the sixth decade of life.¹ Worldwide annual incidence of this neoplasm appears in 11 to 19.6 people per million population.² It is most commonly located in the stomach (51%), but may be found all over the gastrointestinal tract.³

Surgery has been the standard primary treatment of resectable tumor for many years.¹ Recent reports showed that molecular targeted therapy such as tyrosine kinase inhibitors may improve overall survival,^4,5 but nowadays, this is still limited for the treatment of nonresectable, metastatic, or recurrent tumors.¹

It has been shown that advanced age has no influence on GIST surgery outcome.⁶ Moreover, age is not considered to be neither a prognostic factor nor a risk factor in those patients.⁷ However, based solely on the age, less elderly patients with GIST are treated medically and surgically, irrespective of their performance status or comorbidities.⁸

The aim of this study was to evaluate safety, efficacy, and oncologic outcome of surgical treatment in patients older than 75 years.

Materials and Methods

Study was approved by the institutional research ethics committee (Protocol 138-23).

Charts of all patients who underwent surgical treatment due to GIST in Shamir Medical Center from January 1, 2016, to June 31, 2023, were retrospectively reviewed. Database included patient's demographics, indications for surgery (elective or emergency), surgical data, including intraoperative and postoperative complications, and pathology results (tumor size, number of mitoses, ki67%, and involvement of surgical margins).

Patients whose pathology examination did not confirm diagnosis of GIST were not eligible for the study.

Surgical complications were recorded according to Clavien-Dindo classification.⁹

Patients were divided in to 2 groups according to their age. Group 1 included patients younger than 75 years and patients older than 75 years were included in Group 2.

Surgical technique

All patients received intravenous cefazolin prophylaxis 1 hour before incision. All surgeries were performed under general anesthesia. Laparoscopy using a 10 mm 30° camera was used as a default approach either for emergency or elective GIST resection. Exophytic non-gastroesophageal junction (GEJ) and non-pyloric GIST were resected by Echelon^® vascular stapler (Ethicon Ltd.). Endophytic/pyloric/GEJ GIST was removed through gastrotomy with resection by Harmonic^® Scalpel (Ethicon Ltd.), followed by primary closure. The choice to use an open approach was left for tumors larger than 10 cm, emergency or previously operated patients, and location of GIST adjacent to the GEJ. The tumor was removed from the abdomen in an endobag.

Statistical analysis

To compare quantitative (continuous) variables between 2 independent groups, the 2 sample t-test was applied. The association between two categorical variables was assessed using either chi-square or Fisher's exact test. All tests were two tailed, and a P value of .05% or less was considered significant.

Results

Fifty-four patients underwent surgery for suspected GIST during the study period. Five patients were excluded due to pathology results that did not prove the final diagnosis of GIST. Mean age was 69.5 years (ranged 27–91) with equal gender distribution. Most of the patients underwent elective surgery (69.4%). Group 1 included 28 patients and 21 patients were included in Group 2. Mean tumor size was 4.7 cm (range 0.6–18 cm).

Most patients (91.8%) underwent surgery by minimally invasive technique. Mean length of surgery was 77.3 minutes (range 15–246 minutes). Neither intraoperative complications nor blood loss that required blood transfusions was recorded.

Overall postoperative complications rate was 10.2%. Two patients developed severe complications. One of them suffered from missed small bowel injury that required repeated surgery (CD III). Second patient developed a multiorgan failure after emergency surgery for ongoing hemorrhage. Three patients developed mild complications (2 CD II and 1 CD I). Mean length of stay was 4.5 days (range 2–35 days).

Table 1 shows comparison between the groups. Group 2 patients had significantly higher rate of emergency surgery (52.4% versus 14.3%). Four patients (19%) from Group 2 required open surgical approach. The reasons for laparotomy were large tumor size, previous abdominal operations, and poor general condition.

Table 1.

Comparison of Groups' Demographics and Operation Data

	Group 1, <75	Group 2, 75+	P
Number of patients	28	21
Gender
Male	15 (53.6%)	10 (47.6%)	.78
Female	13 (46.4%)	11 (52.4%)	.78
Indication
Elective	24 (85.7%)	10 (47.6%)	.006
Emergency	4 (14.3%)	11 (52.4%)	.006
Operation
LAP	28 (100.0%)	17 (81.0%)	.028
OPEN	0 (0.0%)	4 (19.0%)	.028
Length of operation	74.04 ± 37.78	81.81 ± 57.80	.59
Complications	2 (7.1%)	3 (14.3%)	.64
Length of stay	3 ± 1	6 ± 7	.13

Complete pathologic report was obtained for 88% of patients. Table 2 compares pathology results. Tumor size, number of mitoses, level of ki67%, and involvement of surgical margins were not significantly different. However, tumor size was larger and there was a trend toward higher level of ki67 > 5% in patients from Group 2.

Table 2.

Comparison of Pathological Results

	Group 1, <75 (N = 23)	Group 2, 75+ (N = 20)	P
Tumor size	4.0 ± 1.8	5.5 ± 3.7	.12
Mitoses (in 50 HPF)	2.8 ± 1.7	2.7 ± 1.8	.73
ki67%
<2%	9 (64.3%)	2 (20.0%)	.056
2%–5%	1 (7.1%)	4 (40.0%)
>5%	4 (28.6%)	4 (40.0%)
Clean surgical margins	21 (91.3%)	20 (100.0%)	.11

HPF, high power field.

Discussion

GIST is the most common mesenchymal tumor diagnosed in the gastrointestinal tract with a median patient's age on diagnosis running between 60 and 65 years. Surgical resection with no lymphadenectomy is a worldwide accepted primary treatment for this pathology.¹⁰

In recent years, the life expectancy had increased, reaching a mean age of 79 years,¹¹ which lead to changing of indications to surgical treatment of older patients. This may especially be relevant in less aggressive disease such as GIST as their oncological status may influence life expectance and quality of life.

Previous reports have already mentioned reduced surgical and oncologic intervention among the elderly population,^8,12 emphasizing importance of more liberal approach among this subgroup. The literature so far wondered whether the indication for treatment may even be more extended by the adoption of minimally invasive surgical (MIS) approach for GIST.⁸ Our data show postoperative complication profile (overall 10% of postoperative complications) comparable to published literature.¹³ The oncological benefit is justified as well by the complete R0 resection in more than 90% of the patients.

The need for more aggressive and earlier treatment among the elderly patients is emphasized by large amount of patients who required emergency treatment. Our results show that 50% of patients in this age group were admitted on emergency base compared to 14% among the younger patients group. The delay in treatment of older patients is also reflected by the tendency for larger tumor diameter. Combining the larger tumor diameter with the higher frequency of emergency cases increases the need for open surgery (19% versus 0%) and as a consequence prolong and more complicated recovery among this subgroup.

GIST is a transforming tumor. It was shown that elderly population have a tendency for more aggressive tumor (higher ki67 index and diameter), which might be the result of reported hesitance and delay in surgical intervention for those patients.⁸

This article is a retrospective relatively small case series, harboring lack of standardization in the indications for surgical intervention and missing some of the oncological data. Another drawback is the limited number of cases in each group, which limits the power of the statistical analysis. Although mentioned above, it still points out interesting differences between the groups and it is one of the few studies investigating surgical intervention among elderly patients suffering from GIST in MIS approach era.

Conclusion

Elderly patients tolerate appropriately surgical treatment of GIST, making surgical approach and especially the MIS approach safe and feasible. The MIS intervention reaches the oncological aim of clear surgical margins. The delay in treatment in the older age group might results in increased frequency of emergency cases and higher need for open surgery. Larger prospective randomized trial comparing more early aggressive approach to conservative approach in this specific age group is warranted.

Ethical Approval

This study was approved by the institution's research ethics committee (Protocol 138-23).

Footnotes

Authors' Contributions

Conceptualization: A.B.Y. and Y.H.

Methodology: A.B.Y., Y.H., and I.J.

Formal analysis and investigation: E.M. and J.H.

Writing—original draft preparation: A.B.Y., Y.H., I.J., and J.H.

Writing—review and editing: I.J., A.B.Y., Y.H., and R.L.

Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

References

Akahoshi

, Oya

, Koga

, et al. Current clinical management of gastrointestinal stromal tumor. World J Gastroenterol, 2018; 24,(26):2806–2817.

Corless

. Gastrointestinal stromal tumors: What do we know now?. Mod Pathol, 2014; 27:S1–S16.

Tran

, Davila

, El-Serag

. The epidemiology of malignant gastrointestinal stromal tumors: An analysis of 1,458 cases from 1992 to 2000. Am J Gastroenterol, 2005; 100,(1):162–168.

Demetri

, von Mehren

, Antonescu

, et al. Affiliations expand NCCN Task Force report: Update on the management of patients with gastrointestinal stromal tumors. J Natl Compr Canc Netw, 2010; 8,(Suppl 22):S1–S41.

Cavnar

, Seier

, Curtin

, et al. Outcome of 1000 patients with gastrointestinal stromal tumor (GIST) treated by surgery in the pre- and post-imatinib eras. Ann Surg, 2021; 273,(1):128–138.

Tham

, Poon

, Li

, et al. Gastrointestinal stromal tumour in the elderly. Crit Rev Oncol Hematol, 2009; 70,(3):256–261.

Molinas Mandel

, Selcukbiricik

, Kanitez

, et al. Clinical and pathological characteristics and their effect on survival in elderly patients with gastrointestinal stromal tumors. J BUON, 2016; 21,(2):360–365.

Farag

, van Coevorden

, Sneekes

, et al. Elderly patients with gastrointestinal stromal tumour (GIST) receive less treatment irrespective of performance score or comorbidity—A retrospective multicentre study in a large cohort of GIST patients. Eur J Cancer, 2017; 86:318–325.

Dindo

, Demartines

, Clavien

. Classification of surgical complications: A new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg, 2004; 240,(2):205–213.

10.

Casali

, Blay

, Abecassis

, et al. Gastrointestinal stromal tumours: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 2022; 33,(1):20–33.

11.

Life expectancy at birth. OECD data. 2023. Available from: https://data.oecd.org/healthstat/life-expectancy-at-birth.htm [Last accessed: February 7, 2024].

12.

Dudzisz-Śledź

, Bylina

, Teterycz

, et al. Treatment of metastatic gastrointestinal stromal tumors (GIST): A focus on older patients. Drugs Aging, 2021; 38,(5):375–396.

13.

Huang

C-M

, Chen

Q-F

, Lin

J-X

, et al. Can laparoscopic surgery be applied in gastric gastrointestinal stromal tumors located in unfavorable sites?: A study based on the NCCN guidelines. Medicine (Baltimore), 2017; 96(14):e6535.